Locomotor system broadly containing various organs including bones is responsible for musculoskeletal movements. Exercises such as walking and eating with normal occlusion in daily life are the benefit to maintain the quality of life (QOL) in Japanese super-aged society. To maintain bone health, improvement of lifestyle habit with daily exercise and dietary restriction are needed, and many research studies have been reported that the functional foods can prevent life style related bone diseases. In this review, we introduce the effects of citrus-derived polymethoxyflavonoids on bone diseases.

Citrus-derived polymethoxyflavonoids (PMFs) possess various biological functions such as antioxidative effects, however, the effects of PMFs on bone metabolism remain unclear. Since nobiletin, a one of PMFs, has been reported to clinicoepidemiologically maintain bone mass in 1990s, we have demonstrated basic study for the effects of PMFs including nobiletin. As the results of these sequential studies, polymethoxyflavonoids, such as nobiletin, tangeretin and heptamethoxyflavones, suppressed NF-κB activation, leading to inhibiting osteoclast differentiation through the decrease in PGE₂ production and RANKL expression in osteoblasts.

In this review, we summarized the effects of polymethoxyflabonoids on bone based on the evaluation methodology from cell culture to mass spectrometry imaging of citrus, and discuss the promotion of health through functional foods.

In April 2015, Consumer Affairs Agency (CAA) of Japan launched a new food labeling system known as “Foods with Function Claims (FFC).” Under this notification system, the food industry or an agricultural producer independently evaluates scientific evidence on foods and describes their functional properties. As of March 16, 2020, 2,801 FFC had been registered, including the following agricultural products (62 items) or the foods with low-order processing, mandarin orange, soybean sprouts, apples, melon, grape, banana, tomato, Enoki mushroom, amberjack, yellowtail, egg, kale, spinach, pepper, melon, chicken breast, pork, and green tea, frozen spinach, steamed soybeans, barley, rice, herring roe, agar.

The guidelines of FFC were revised in March 2019. The major modifications related to fresh foods are as follows:

The labeling of the partial intake (50% or more) of the daily intake of functional ingredients in fresh food was accepted, the confirmation of registration has become faster, the ingredients for registration expanded, the range of handling data for mild patients and the confirmation process in the CAA has been clarified when a functional ingredient of a fresh food or processed foods is included in the "exclusively pharmaceutical list".

In the future development of fresh food as FFC, it has some challenges in the development of control technology of functional components variation during cultivation and processing, the development of 100% inspection system, the evaluation method of hybrid functionality, the consumer education for adequate eating functional foods and the providing of correct information to consumers.

Mitochondria are the site of aerobic energy production and the base of production of reactive oxygen species (ROS). Age-related decline in mitochondrial function is a target of anti-aging research because it affects cell fate. Superoxide (O₂·-), the base substance of ROS generated by physiological oxygen metabolism in mitochondria, is promptly treated by the catalytic action of superoxide dismutase (SOD). In the cell, SOD1 is constitutively localized in the cytoplasm and SOD2 in the mitochondrial matrix, respectively, and the intracellular O₂·- level is appropriately maintained. Analyses using genetically engineered mice revealed that disruption of redox regulation due to cytoplasmic SOD1 or mitochondrial SOD2 deficiencies causes cell death and senescence-like phenotypes in cells, leading to atrophy and dysfunction in various organs throughout the body. Since both mouse models exhibit premature aging and age-related diseases, they are aging model mice based on oxidative damage. In addition, since the models also show clear age-related organ phenotypes, it is considered possible to scientifically evaluate drugs and food factors. In this review, I would like to introduce the latest knowledge of model mice and specific examples of functional food factors, and discuss the possibility of aging control.

The knee osteoarthritis (knee OA) model has been reported to be a spontaneous model and a traumatic model. Both models have merits and demerits, and it is important to use a model that suits the experiment. In our laboratory, we report studies in which the administration of collagen hydrolysate affected the OA symptom. It is shown that the effect may be due to collagen-specific peptides that have been transferred to the blood.

The number of elderly people aged 65 years and older has been increasing worldwide, and the aging of the population is particularly rapid in Japan. In 2007, the Japanese Orthopaedic Association(JOA) proposed the concept of “locomotive syndrome (Locomo),” which refers to the conditions under which people require or may soon require nursing-care services because of problems with the locomotor organs (muscle, joints and bones). As a result, there has been increasing interest in preventing "locomo" by improving lifestyle, mainly eating habits and/or exercise habits.

And with the launch the system of "Foods with function Claims", the development of foods with health claims based on scientific evidences have attracted attention. We are focusing on research of aging in locomotor organs (muscle, joints and bones). In particular, we focus on obtaining evidences of the effectiveness of glucosamine-containing foods in humans. In this article, we would like to introduce the foods containing glucosamine with functional claim focusing on knee joint function and walking speed.

The pandemic of COVID-19 caused by the novel coronary virus (SARS-CoV-2) infection has caused a great impact on socio-economic activities worldwide. As for the risk-reduction of COVID-19, it is essential to take measures to reduce the exposure to the SARS-CoV-2 virus as well as to increase the resistance to infection in the human host. This review reported that functional food ingredients have antiviral, immunomodulatory, and anti-inflammatory effects. Numerous studies showed the efficacy of dietary supplements contains these food components to prevent and reduce the severity of viral respiratory infections. There are still many unclear points regarding the susceptibility of the virus infection and the aggravation of COVID-19. It is suggested that the ʻcytokine stormʼ is involved in the process of COVID-19 aggravation. There are functional food materials which act to regulate cytokine production. This is a narrative review of the evidence of functional food ingredients for COVID-19 prophylaxis.

The nations are concerning to prevent lifestyle diseases by daily dietary food consumption in a super-aged society of Japan. Functional food components such as carotenoids and flavonoids possess various beneficial effects including anti-oxidative effects for human health. Liquid chromatography-mass spectrometry (LC-MS) are widely applied to the quantitative analysis of many agricultural products. Recently, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is developed as a novel technique. MSI is a direct mass spectrometric analysis of the tissue surface and can visualize the distribution of target molecules such as phospholipids and small biomolecules on tissue sections of agricultural products. In the present study, we analyzed the distribution of functional compounds on the sections of mini tomato by MSI. Our findings indicate that MS imaging technique can be applied to the detection of functional compound, freshness evaluation and residual chemicals for various agricultural products.

Theobromine, a methylated derivative of xanthines, is included in some plants such as cocoa beans, tea and guarana. A recent in vitro study reported that theobromine possibly promotes osteoblast differentiation from mesenchymal stem cell (MSC). In this study, we investigated the effects of theobromine feeding to mice on the bone density and the proliferation and differentiation of MSC and hematopoietic stem cell (HSC) of the mice.

C57BL/6J mice were fed a normal diet (ND) and 0.05% theobromine-containing diet (TBD) for 4 weeks. The tibias of the mice were dissected to measure the bone mineral density. The MSCs and HSCs were collected from the bone marrow fluids. The proliferation ability, the ability of the MSCs to differentiate to osteoblasts and the ability of the HSCs to differentiate to osteoclasts were evaluated. The theobromine concentration of the bone marrow fluids was analyzed by an LC-MS/MS method.

The cortical bone density of the TBD group was significantly higher than that of the ND group. The proliferation and differentiation abilities of the MSCs from the TBD group significantly surpassed those from the ND group. The differentiation ability of the HSCs from the TBD group tended to be lower than that from the ND group (p = 0.1055). Theobromine was detected only in the TBD group at the concentration of 18.9 ± 5.6 pg/mL.

These results suggest that continuous intake of theobromine possibly increased the bone density by promoting the osteoblast proliferation and differentiation and suppressing the osteoclast differentiation.

Storage of vegetables and fruits for long durations inactivates important enzymes and degrades useful components such as vitamin C. An effective method of preservation bypassing these issues is by fermentation.The enzyme syrup extracted from fermented fruits and vegetables is presumed to have high concentrations of effective components. In this study, we investigated the cancer cell growth inhibitory, anti-oxidant, and α-glucosidase inhibitory effects of enzyme syrup obtained by fermenting apples. Moreover, we aimed to identify the microorganism responsible for fermentation.

Apples were sliced and stored with 1.1 times sugar in a glass container for 2 weeks. Enzyme syrup was extracted after 7 and 14 days.

To assess cancer cell growth inhibitory effects of the enzyme syrup, leukemia cell line P388 was grown in syrup or sterilized water at 37°C, 5.0% CO₂ for 7 days, after which the amount of P388 in each medium was compared. To assess anti-oxidant effect, DPPH radical-scavenging activity was checked. Further, to test α-glucosidase inhibitory effects, α-glucosidase inhibiting activity was investigated. To identify the microorganism responsible for fermentation, enzyme syrup was spread onto a standard agar plate and incubated at 35°C for 2 days. The DNA of the resultant colonies was analyzed.

As observed, cell growth was suppressed with both 7 and 14 day fermented syrup. However, the anti-oxidant activity of the syrup was lower than that of apple extract. Furthermore, fermented syrup had high α-glucosidase inhibiting activity. The microorganism was identified as Metschnikowia pulcherrima in 97% of the colonies. To conclude, we found that apple fermented enzyme syrup has cancer cell growth inhibitory and α-glucosidase inhibitory activity.

To conclude, we found that apple fermented enzyme syrup has cancer cell growth inhibitory and α-glucosidase inhibitory activity.

Retinitis pigmentosa(RP) is an ophthalmic disease eventually leading to blindness. There is no fundamental cure. In RP there is apoptosis of photoreceptor cells caused by oxidative stress. Suppressive effects from acerola water (AW) on N-methyl-N-nitrosourea (MNU) -induced retinal degeneration in rats and hereditary retinal degeneration in C3H mice were examined experimentally. Female SD rats at 7 weeks of age were given a single i.p. injection of 50 mg/kg MNU. Distilled water (DW), and 4% or 8% AW was orally administered once daily (2mL/ rat) from 3 days before MNU injection until the day of necropsy. Eyes were collected 7 days after MNU treatment and photoreceptor cell and retinal damage ratios were calculated. The peripheral retinal photoreceptor cell ratio was significantly higher in the MNU+8%AW group compared to the MNU treated group. In eyes collected 10 or 24 hrs after MNU, immunohistochemical and TUNEL staining resulted in significantly lower numbers of γH2AX and HO-1 positive photoreceptor cells in the MNU+8%AW group 24hrs after MNU. In C3H mice given i.p. injections of DW or 4%AW (0.1mL/mouse) every other day or every day from 8 days of age until the day of necropsy, the peripheral retinal photoreceptor cell ratio was significantly higher in the 4%AW daily treated group at 13 days of age. These results confirm the suppressive effects of AW in different RP animal models. The mode of action is suggested to be suppression of retinal oxidative stress. AW could potentially be effective in suppressing of human RP.

Retinitis pigmentosa (RP) is an ophthalmic disease with no fundamental cure that eventually leads to blindness. Since RP is associated with apoptosis of photoreceptor cells caused by oxidative stress, suppression of oxidative stress is expected to be effective in ameliorating RP. Since black soybean seed coat extract has high antioxidant activity, we used Chrono-Care^® (Chrono-Care ^® SP60, Fujicco Co., Ltd.) that contains black soybean polyphenol to investigate suppressive effects on N-methyl-N-nitorsourea (MNU) -induced retinal degeneration in rats. The antioxidant effects of 1, 2, and 4% Chrono-Care^® water were measured by an OXY-adsorbent test. Female SD rats at 7 weeks of age were given a single i.p. injection of 50 mg/kg MNU and 0.2 or 2% Chrono Care ^® -containing diets were freely fed from 4 weeks of age until the day of necropsy. Eyes were collected 48 hrs after MNU injection and the photoreceptor cell ratio was calculated. Using the same animal model, rats were freely fed 2% diet on the same schedule. Eyes were collected 24 hrs and 7 days after MNU injection for TUNEL and other immunostaining. In the results, concentration-dependent increase of antioxidant activity was observed. In the 2% diet combined group, retinal photoreceptor cell ratio was higher than in the MNU treated group. In the 2% diet combined group, TUNEL and anti-thymidine glycol immunostaining signals were lower than in the MNU treated group 24 hrs after MNU injection. Rhodopsin positive immunostaining was extensive in outer retina 7 days after MNU injection. In conclusion, suppressive effects of Chrono-Care ^® SP60 on MNU induced retinal degeneration was demonstrated. The mode of action is potentially related to the suppression of oxidative stress in the retina. It may possibly be effective in suppressing of human RP.

Background: In the field of public health, Public-Private Partnerships (PPPs) have become possible modalities in conducting health promotion policies. Sakai-Town, Ibaraki Prefecture, and DHC Corporation signed a comprehensive cooperation agreement with the aim of revitalizing the local community and promoting the health of residents.

Purpose: To evaluate the efficacy and feasibility of a weight loss intervention program by Sakai-Town as PPPs.

Methods: Overweight or obese subjects, otherwise healthy, participated in the weight loss program, using telephone and/or personalized web site to receive individual dietary counseling from medical professionals. Meal replacements, ‘DHC Protein Diet' series, were consumed once daily instead of regular meals. A typical product contains 20.1g of protein, one-third of the RDA (recommended dietary allowance) of vitamins and minerals, and other functional food ingredients in 1 bag gross weight 50 g or 167 kcal. Anthropometric parameters and body composition were assessed before and after the 12-week weight-loss program.

Results: Eighty-seven participants (male 42, female 45, mean age 47.2 years) completed the 12-week program. Compared with the baseline, the significant decreases in BMI, body weight and waist circumference were observed.

Conclusion: The result demonstrated that a technology-based intervention, combined with meal replacements was effective and feasible for reducing body weight in obese subjects as health policy by a local government with PPPs. Health care companies should play a pivotal role in realizing a healthy longevity society.